What is the appropriate outpatient evaluation and initial management for a 61‑year‑old woman with no past medical history who is being assessed for possible hypertrophic cardiomyopathy?

Outpatient Evaluation for Suspected Hypertrophic Cardiomyopathy

Order a comprehensive transthoracic echocardiogram immediately as the cornerstone diagnostic test, obtain a 12-lead ECG and 24-hour Holter monitor, and collect a detailed 3-generation family history focusing on sudden cardiac death and HCM. 1

Initial Diagnostic Testing

Transthoracic Echocardiography (Priority #1)

• TTE is the Class I recommendation for initial evaluation of all patients with suspected HCM and should assess wall thickness, distribution of hypertrophy, presence of left ventricular outflow tract obstruction (LVOTO), systolic anterior motion (SAM) of the mitral valve, and diastolic function. 1
• Diagnostic criteria require LV wall thickness ≥15 mm in adults that cannot be explained by loading conditions alone (hypertension, aortic stenosis). 1, 2
• Perform provocative maneuvers during the echocardiogram (Valsalva, squat-to-stand, or simply standing) to unmask dynamic LVOTO, as resting gradients underestimate obstruction in approximately 50% of cases. 1, 2
• If resting gradient is <50 mmHg but symptoms suggest obstruction, order exercise echocardiography as the most physiologic provocation method. 1, 2

12-Lead Electrocardiogram

• The ECG is abnormal in 75-95% of HCM patients and may show LV hypertrophy with strain pattern, deep Q waves mimicking myocardial infarction, or patterns suggesting phenocopies like Fabry disease or amyloidosis. 1, 2
• ECG abnormalities do not correlate with severity or pattern of hypertrophy but are essential for baseline documentation. 1

24-Hour Holter Monitoring

• Holter monitoring is critical for sudden cardiac death risk stratification as it detects non-sustained ventricular tachycardia (NSVT), which identifies patients at significantly higher risk. 1, 2
• This should be obtained during initial evaluation, not deferred. 2

Comprehensive Clinical Assessment

History Taking (3-Generation Family History)

• Document any relatives with HCM or unexpected/sudden death at young age (<50 years), as family history of premature sudden cardiac death is a major risk factor. 1, 2
• Assess symptoms: dyspnea, chest pain, palpitations, syncope (unexplained syncope is a high-risk feature), and exercise tolerance. 1
• Screen for syndromic features suggesting phenocopies: ataxia, hearing loss, visual impairment, cognitive dysfunction, or failure to thrive (may indicate metabolic storage diseases like Fabry, Danon, or Pompe disease). 1

Physical Examination with Provocative Maneuvers

• Auscultate for harsh crescendo-decrescendo systolic murmur at lower left sternal border that increases with Valsalva or standing (worsens LVOTO) and decreases with squatting (reduces LVOTO). 1
• Palpate for prominent/displaced apical impulse, assess carotid pulse character (brisk upstroke in obstructive HCM), and listen for S4 gallop. 1
• Perform bedside provocative maneuvers (Valsalva, squat-to-stand, passive leg raising) to assess dynamic changes in murmur intensity. 1

Risk Stratification for Sudden Cardiac Death

Identify the following high-risk features during initial evaluation:

• Maximal wall thickness ≥30 mm (massive hypertrophy with linear association with sudden death risk) 2
• NSVT on Holter monitoring (≥3 consecutive ventricular beats at ≥120 bpm) 1, 2
• Family history of premature sudden cardiac death from HCM 2
• Unexplained syncope (particularly if recent or recurrent) 2
• LV apical aneurysm (may require cardiac MRI to detect if small) 1, 2

When to Order Cardiac MRI

Consider CMR when:

• Echocardiography is technically limited or inconclusive (poor acoustic windows, obesity). 1, 2
• Suspected apical HCM or apical aneurysm, as these are poorly visualized by echocardiography but clearly seen on CMR. 1, 2
• Hypertrophy involves anterolateral free wall, where echocardiography may underestimate wall thickness by several millimeters compared to CMR. 1
• Suspicion for infiltrative disease (amyloidosis, Fabry disease, sarcoidosis) based on clinical features—CMR with late gadolinium enhancement can identify specific patterns. 2, 3

Critical Differential Diagnoses to Exclude

Hypertensive Heart Disease

• Long-standing hypertension can produce concentric LVH that overlaps phenotypically with HCM, but typically shows symmetric/concentric pattern rather than asymmetric septal hypertrophy. 1, 2
• In a 61-year-old with no documented hypertension history, this is less likely but must be considered. 1

Infiltrative Cardiomyopathies

• Cardiac amyloidosis (AL or transthyretin-type) presents with concentric LVH, "sparkling" myocardial texture, thickened interatrial septum, thickened AV valves, and small pericardial effusion on echo. 1, 3
• Fabry disease should be considered, particularly in women, with concentric LVH and associated systemic features. 1
• Order serum and urine protein electrophoresis with immunofixation if amyloidosis suspected; consider alpha-galactosidase A levels for Fabry disease. 3

Athlete's Heart

• Less relevant in a 61-year-old woman with no athletic history, but physiologic remodeling from exercise can produce mild LVH (typically <13 mm, symmetric, with normal diastolic function). 1

Immediate Management Considerations

Medications to Avoid

• Do not prescribe vasodilators (ACE inhibitors, ARBs, nitrates), high-dose diuretics, or digoxin if obstructive HCM is confirmed, as these worsen LVOTO. 2
• Avoid dehydration and volume depletion. 2

Activity Restrictions

• Pending full evaluation, advise against high-intensity competitive sports or strenuous isometric exercise until risk stratification is complete. 1

Follow-Up Testing Schedule

• Repeat TTE every 1-2 years in clinically stable patients to monitor for progression of hypertrophy, development of obstruction, or systolic/diastolic dysfunction. 1, 2
• Repeat Holter monitoring every 1-2 years in patients without ICDs to screen for development of NSVT. 1, 2
• Annual 12-lead ECGs to monitor for rhythm changes, particularly atrial fibrillation. 2

Family Screening Protocol

If HCM is confirmed:

• All first-degree relatives require ECG and echocardiographic screening. 1
• For relatives aged 12-21 years: screen every 12-18 months (earlier if competitive athlete, symptoms develop, or malignant family history). 1
• For adult relatives (>21 years): screen every 5 years or sooner if symptoms develop. 1
• Genetic testing may identify pathogenic variants, allowing mutation-negative relatives to discontinue screening. 1

Common Pitfalls to Avoid

• Do not assume all LVH is from hypertension in any patient without documented long-standing severe hypertension—HCM affects 1:500 people and is likely underdiagnosed. 2, 4
• Do not perform echocardiography without provocative maneuvers—resting gradients miss dynamic LVOTO in half of cases. 1, 2
• Do not overlook family screening—HCM is inherited in an autosomal dominant pattern, and first-degree relatives have 50% chance of carrying the mutation. 1
• Do not miss apical HCM—this variant is easily overlooked on standard echocardiography due to near-field artifacts and may require contrast echocardiography or CMR. 1

Referral Considerations

• Consider referral to or consultation with an HCM center for complex management decisions, particularly if high-risk features are present, symptoms are refractory, or invasive septal reduction therapy is being considered. 1